September 27, 2013

Researchers Find Brain Circuitry That Triggers Binge Eating

Researchers at University of North Carolina have identified a part of the brain that may play a critical role in eating disorders such as anorexia and bulimia.

The scientists were able to pinpoint the precise cellular connections responsible for triggering this behavior, something that could give insight into a potential cause of obesity and perhaps lead to better treatments for anorexia, bulimia, and binge eating disorder – the most common eating disorders in the United States. The study could also eliminate some of the stigmatizing explanations that these disorders are often attributed to, such as a lack of willpower.

"The study underscores that obesity and other eating disorders have a neurological basis," said senior study author Garret Stuber, PhD, assistant professor in the departments of psychiatry, cell biology and physiology at UNC and a member of the UNC Neuroscience Center.

"With further study, we could figure out how to regulate the activity of cells in a specific region of the brain and develop treatments.”

Sixty years ago, scientists found they could electrically stimulate a region of a mouse's brain called the lateral hypothalamus and cause the mouse to eat, whether hungry or not. However, these stimulations were actually being applied to many different types of brain cells.

Stuber wanted to focus on one specific cell type – gaba neurons in the bed nucleus of the stria terminalis, or BNST. The BNST is an outcropping of the amygdala, the part of the brain associated with emotion. The BNST also forms a bridge between the amygdala and the lateral hypothalamus, the brain region that drives primal functions such as eating, sexual behavior, and aggression.

The BNST gaba neurons have a cell body and a long strand with branched synapses that transmit electrical signals into the lateral hypothalamus. Stuber and colleagues wanted to stimulate those synapses using an optogenetic technique, a complex process that would stimulate BNST cells simply by shining light on their synapses.

Typically, brain cells don't respond to light. So Stuber's team used genetically engineered proteins from algae, which are sensitive to light and used genetically engineered viruses to deliver them into the brains of mice. Those proteins then get expressed only in the BNST cells, including in the synapses that connect to the hypothalamus.

The researchers then implanted fiber optic cables in the brains of these specially-bred mice, allowing them to shine light through the cables and onto BNST synapses. They found that as soon as the light hit BNST synapses, the mice began to eat voraciously, even though they were well fed. Furthermore, the mice showed a strong preference for high-fat foods.

"They would essentially eat up to half their daily caloric intake in about 20 minutes," Stuber said. "This suggests that this BNST pathway could play a role in food consumption and pathological conditions such as binge eating."

Stimulating the BNST also led the mice to exhibit behaviors associated with reward, suggesting that shining light on BNST cells enhanced the pleasure of eating. The study also found that shutting down the BNST pathway caused mice to show little interest in eating, even if they had been deprived of food.

"We were able to really hone in on the precise neural circuit connection that was causing this phenomenon that's been observed for more than 50 years," Stuber said.

The research suggests that faulty wiring in BNST cells could interfere with hunger or satiety cues and contribute to human eating disorders, leading people to eat even when they are full or to avoid food when they are hungry.

The scientists said additional research is needed to determine whether it would be possible to develop drugs that correct a malfunctioning BNST circuit.

"We want to actually observe the normal function of these cell types and how they fire electrical signals when the animals are feeding or hungry," Stuber said.

"We want to understand their genetic characteristics - what genes are expressed. For example, if we find cells that become really activated after binge eating, can we look at the gene expression profile to find out what makes those cells unique from other neurons."

Such research could lead to potential targets for drugs to treat certain populations of patients with eating disorders, he said.

A report of the team's findings are published in the September 27 edition of the journal Science.